Interfering with DNA Damage Signals: Radiosensitizing Prostate Cancer using Small Peptides
Abstract
We aimed to identify small peptides that can target critical DNA damage responsive pathways in order to develop novel therapeutic agents that can sensitize prostate cancer cells to radiotherapy. Critical DNA damage pathways determining cellular radiosensitivity is medicated by ATM and its phosphorylation of downstream targets including Structural Maintenance of Chromosomal protein one (SMC1) and Nijmegen Breakage Syndrome protein 1 (NBS1). We have demonstrated that small fusion peptides containing SMC1 phosphorylation sequences can inhibit ATM activity. We have characterized the inhibitory effect of the THM-SMC1 peptide on cellular responses to radiation and found the peptide can abolish radiation induced S-phase checkpoint and decrease prostate tumor cell clonogenic survival. During the last performance period we have studied the molecular mechanisms of SMC1 peptide-induced radiosensitization. We have also identified a novel inhibitory peptide containing the NBS1 C-terminal conserved sequence. The NBS1 inhibitory peptides (NIP) can increase prostate cancer cellular radiosensitivity. Future directions include in vivo evaluation of the fusion peptides as powerful radiosensitizers in prostate cancer xenograft models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2007
- Accession Number
- ADA489667
Entities
People
- Bo Xu
Organizations
- Louisiana State University